Epigallocatechin-3-gallate attenuates PAR-2–mediated inflammatory signaling and preserves markers of mitochondrial integrity in osteoarthritic chondrocytes
- 1College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai Health, Dubai, United Arab Emirates.
Abstract
Epigallocatechin-3-gallate (EGCG), the principal catechin of green tea, exhibits broad anti-inflammatory properties; however, its effect on protease-activated receptor-2 (PAR-2)–mediated signaling in osteoarthritis (OA) has not been investigated. Here, we report that EGCG (5–10 µM) dose-dependently suppresses PAR-2 expression at both mRNA and protein levels in lipopolysaccharide (LPS)-stimulated human chondrocytes derived from bone marrow mesenchymal stem cells. This upstream inhibition attenuated ERK1/2 phosphorylation (pERK/total ERK ratio reduced below basal levels at 10 µM) and produced concordant suppression of three functionally linked effector arms: (i) pro-inflammatory cytokines (TNF-α, IL-1β, MCP-1), with near-maximal inhibition at 10 µM and a saturation plateau at 20 µM; (ii) the SOX4–ADAMTS-5 catabolic axis (81.9% and 66.2% protein reduction, respectively); and (iii) RANK/RANKL surface expression. EGCG also restored mitochondrial membrane potential and biomass to near-homeostatic levels. Crucially, small interfering RNA (siRNA)-mediated PAR-2 silencing reduced LPS-induced TNF-α by ~38% and substantially blunted EGCG’s incremental efficacy, supporting PAR-2 as a predominant, though not exclusive, mediator of EGCG’s anti-inflammatory action. The effective concentrations employed are physiologically attainable through dietary green tea consumption, as documented by a comprehensive survey of EGCG content across 36 commercial varieties. These findings support PAR-2 as a candidate upstream target of EGCG in OA chondrocytes and suggest a mechanistic model involving PAR-2 → ERK1/2 → TNF-α/SOX4/ADAMTS-5, through which a dietary polyphenol exerts coordinated anti-inflammatory and anti-catabolic effects, while preserving structural and thermodynamic markers of mitochondrial integrity.
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BibTeX
@article{patnaik2026epigallocatechin3gallate,
title = {{Epigallocatechin-3-gallate attenuates PAR-2–mediated inflammatory signaling and preserves markers of mitochondrial integrity in osteoarthritic chondrocytes}},
author = {Rajashree Patnaik and Yajnavalka Banerjee},
journal = {PLOS One},
year = {2026},
month = nov,
doi = {10.1371/journal.pone.0357766},
url = {https://doi.org/10.1371/journal.pone.0357766},
note = {CC BY},
}
RIS
TY - JOUR
TI - Epigallocatechin-3-gallate attenuates PAR-2–mediated inflammatory signaling and preserves markers of mitochondrial integrity in osteoarthritic chondrocytes
AU - Rajashree Patnaik
AU - Yajnavalka Banerjee
PY - 2026
DA - 2026/11/02
JO - PLOS One
DO - 10.1371/journal.pone.0357766
UR - https://doi.org/10.1371/journal.pone.0357766
AB - Epigallocatechin-3-gallate (EGCG), the principal catechin of green tea, exhibits broad anti-inflammatory properties; however, its effect on protease-activated receptor-2 (PAR-2)–mediated signaling in osteoarthritis (OA) has not been investigated. Here, we report that EGCG (5–10 µM) dose-dependently suppresses PAR-2 expression at both mRNA and protein levels in lipopolysaccharide (LPS)-stimulated human chondrocytes derived from bone marrow mesenchymal stem cells. This upstream inhibition attenuated ERK1/2 phosphorylation (pERK/total ERK ratio reduced below basal levels at 10 µM) and produced concordant suppression of three functionally linked effector arms: (i) pro-inflammatory cytokines (TNF-α, IL-1β, MCP-1), with near-maximal inhibition at 10 µM and a saturation plateau at 20 µM; (ii) the SOX4–ADAMTS-5 catabolic axis (81.9% and 66.2% protein reduction, respectively); and (iii) RANK/RANKL surface expression. EGCG also restored mitochondrial membrane potential and biomass to near-homeostatic levels. Crucially, small interfering RNA (siRNA)-mediated PAR-2 silencing reduced LPS-induced TNF-α by ~38% and substantially blunted EGCG’s incremental efficacy, supporting PAR-2 as a predominant, though not exclusive, mediator of EGCG’s anti-inflammatory action. The effective concentrations employed are physiologically attainable through dietary green tea consumption, as documented by a comprehensive survey of EGCG content across 36 commercial varieties. These findings support PAR-2 as a candidate upstream target of EGCG in OA chondrocytes and suggest a mechanistic model involving PAR-2 → ERK1/2 → TNF-α/SOX4/ADAMTS-5, through which a dietary polyphenol exerts coordinated anti-inflammatory and anti-catabolic effects, while preserving structural and thermodynamic markers of mitochondrial integrity.
SN - 1932-6203
ER -